In vitro--in vivo correlation, a time scaling problem? Basic considerations on in vitro dissolution testing

Abstract

The profile of cumulative amount released from a solid dosage form, observed in an in vitro liberation apparatus, represents the cumulative frequency of the residence times of drug molecules in the galenic formulation. The profile of release over time is usually affected by the dissolution models as well as by the experimental conditions. Such differing dissolution curves may become superimposable by a simple linear transformation of the time base. This is clearly demonstrated by two completely different retard formulations, film coated pellets and an erosible matrix tablet, which were tested in two dissolution apparatus, the Sartorius dissolution model and the USP-Paddle model. The parameters used in the transformation of the time base can be evaluated from the statistical moments of the residence times; the moments themselves are calculated from the cumulative frequency functions. The term "equivalence" of dissolution profiles is defined and discussed. The outlined considerations and methods are immediately transferable to the comparison of in vitro and in vivo liberation conditions.